TY  - JOUR
AU  - Mogler, Carolin
AU  - Wieland, Matthias
AU  - König, Courtney
AU  - Hu, Junhao
AU  - Runge, Anja
AU  - Korn, Claudia
AU  - Besemfelder, Eva
AU  - Breitkopf-Heinlein, Katja
AU  - Komljenovic, Dorde
AU  - Dooley, Steven
AU  - Schirmacher, Peter
AU  - Longerich, Thomas
AU  - Augustin, Hellmut
TI  - Hepatic stellate cell-expressed endosialin balances fibrogenesis and hepatocyte proliferation during liver damage.
JO  - EMBO molecular medicine
VL  - 7
IS  - 3
SN  - 1757-4684
CY  - Weinheim
PB  - Wiley-VCH
M1  - DKFZ-2017-03191
SP  - 332 - 338
PY  - 2015
AB  - Liver fibrosis is a reversible wound-healing response to injury reflecting the critical balance between liver repair and scar formation. Chronic damage leads to progressive substitution of liver parenchyma by scar tissue and ultimately results in liver cirrhosis. Stromal cells (hepatic stellate cells [HSC] and endothelial cells) have been proposed to control the balance between liver fibrosis and regeneration. Here, we show that endosialin, a C-type lectin, expressed in the liver exclusively by HSC and portal fibroblasts, is upregulated in liver fibrosis in mouse and man. Chronic chemically induced liver damage resulted in reduced fibrosis and enhanced hepatocyte proliferation in endosialin-deficient (EN(KO)) mice. Correspondingly, acute-liver-damage-induced hepatocyte proliferation (partial hepatectomy) was increased in EN(KO) mice. A candidate-based screen of known regulators of hepatocyte proliferation identified insulin-like growth factor 2 (IGF2) as selectively endosialin-dependent hepatocyte mitogen. Collectively, the study establishes a critical role of HSC in the reciprocal regulation of fibrogenesis vs. hepatocyte proliferation and identifies endosialin as a therapeutic target in non-neoplastic settings.
KW  - Antigens, CD (NLM Chemicals)
KW  - Antigens, Neoplasm (NLM Chemicals)
KW  - CD248 protein, human (NLM Chemicals)
KW  - Neoplasm Proteins (NLM Chemicals)
KW  - tumor endothelial marker 1, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25680861
C2  - pmc:PMC4364949
DO  - DOI:10.15252/emmm.201404246
UR  - https://inrepo02.dkfz.de/record/127165
ER  -